11-Deoxy-11-hydroxymethyl-6-hydroxy-PGE1 compounds

ABSTRACT

The present invention provides 11-deoxy-11-hydroxymethyl-6-hydroxy-PGE 1  compounds which are useful pharmacological agents. These analogs are useful as prostacyclin-like drugs.

CROSS REFERENCE TO RELATED APPLICATION

This application is a continuation-in-part of Ser. No. 812,794, July 5, 1977, now issued as U.S. Pat. No. 4,131,738.

The present invention relates to 11-deoxy-11-hydroxymethyl-6-hydroxy-PGE₁ compounds, the preparation and use of which are described in U.S. Ser. No. 812,794, filed July 5, 1977, now issued as U.S. Pat. No. 4,131,738 on Dec. 26, 1978.

The essential material constituting a disclosure of the instant invention is incorporated by reference here from U.S. Pat. No. 4,131,738. 

I claim:
 1. A prostacyclin analog of the formula ##STR1## wherein Z₁ is (1) --(CH₂)_(g) --CH₂ --CH₂ --,(2) --(ch₂)_(g) --CH₂ --CF₂ --, or (3) trans--(CH₂)_(g) --CH═CH--,wherein g is the integer one, 2, or 3; Wherein Y₁ is (1) trans--CH═CH--, (2) cis--CH═CH--, (3) --ch₂ ch₂ --, (4) trans--CH═C(Hal)--, or (5) --C.tbd.C--,wherein Hal is chloro or bromo; Wherein M₁ is ##STR2## wherein R₅ is hydrogen or alkyl with one to 4 carbon atoms, inclusive; Wherein L₁ is ##STR3## wherein R₃ and R₄ are hydrogen, methyl, or fluoro, being the same or different, with the proviso that one of R₃ and R₄ is fluoro only when the other is hydrogen or fluoro; Wherein R₁ is hydrogen; alkyl of one to 12 carbon atoms, inclusive; cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbon atoms, inclusive; phenyl; phenyl substituted with one, two, or three chloro or alkyl of one to 3 carbon atoms; phenyl substituted in the para position by ##STR4## WHEREIN R₂₅ is methyl, phenyl, acetamidophenyl, benzamidophenyl, or --NH₂ ; R₂₆ is methyl, phenyl, --NH₂, or methoxy; and R₂₇ is hydrogen or acetamido, inclusive; or a pharmacologically acceptable cation; wherein m is the integer one to 5, inclusive.
 2. A prostacyclin analog according to claim 1, wherein ˜OH is beta.
 3. 11-Deoxy-11-hydroxymethyl-6β-hydroxy-PGE₁, a prostacyclin analog according to claim
 2. 4. A prostacyclin analog according to claim 1, wherein ˜OH is alpha.
 5. 11-Deoxy-11-hydroxymethyl-6α-hydroxy-PGE₁, a prostacyclin analog according to claim
 4. 6. 11-Deoxy-11-hydroxymethyl-6α-hydroxy-15-methyl-PGE₁, a prostacyclin analog according to claim
 4. 7. 11-Deoxy-11-hydroxymethyl-6α-hydroxy-16,16-dimethyl-PGE₁, a prostacyclin analog according to claim
 4. 8. 11-Deoxy-11-hydroxymethyl-6α-hydroxy-16,16-difluoro-PGE₁, a prostacyclin analog according to claim
 4. 9. A prostacyclin analog according to claim 1, wherein ˜OH is a mixture of α-OH and β-OH.
 10. A prostacyclin analog according to claim 9, wherein Y₁ is cis--CH═CH--.
 11. 11-Deoxy-11-hydroxymethyl-6-hydroxy-cis-13-PGE₁, a prostacyclin analog according to claim
 10. 12. A prostacyclin analog according to claim 9, wherein Y₁ is --C.tbd.C--.
 13. 11-Deoxy-11-hydroxymethyl-6-hydroxy-13,14-didehydro-PGE₁, a prostacyclin analog according to claim
 12. 14. A prostacyclin analog according to claim 9, wherein Y₁ is trans--CH═C(Hal)--.
 15. 11-Deoxy-11-hydroxymethyl-6-hydroxy-14-chloro-PGE₁, a prostacyclin analog according to claim
 14. 16. A prostacyclin analog according to claim 9, wherein Y₁ is --CH₂ CH₂ --.
 17. 11-Deoxy-11-hydroxymethyl-6-hydroxy-13,14-dihydro-PGE₁, a prostacyclin analog according to claim
 16. 18. A prostacyclin analog according to claim 9, wherein Y₁ is trans-CH═CH--.
 19. A prostacyclin analog according to claim 18, wherein Z₁ is --(CH₂)_(g) --(CH₂ --CF₂ --.
 20. 11-Deoxy-11-hydroxymethyl-2,2-difluoro-6-hydroxy-15-methyl-PGE₁, a prostacyclin analog according to claim
 19. 21. A prostacyclin analog according to claim 18, wherein Z₁ is trans--(CH₂)_(g) --CH═CH--.
 22. 11-Deoxy-11-hydroxymethyl-trans-2,3-didehydro-6-hydroxy-PGE₁, a prostacyclin analog according to claim
 21. 23. A prostacyclin analog according to claim 18, wherein Z₁ is --(CH₂)_(g) --CH₂ --CH₂ --.
 24. A prostacyclin analog according to claim 23, wherein g is one.
 25. A prostacyclin analog according to claim 24, wherein m is
 3. 26. A prostacyclin analog according to claim 25, wherein R₅ is methyl.
 27. 11-Deoxy-11-hydroxymethyl-6-hydroxy-15-methyl-PGE₁, a prostacyclin analog according to claim
 26. 28. A prostacyclin analog according to claim 25, wherein R₅ is hydrogen.
 29. A prostacyclin analog according to claim 28, wherein at least one of R₃ and R₄ is fluoro.
 30. 11-Deoxy-11-hydroxymethyl-6-hydroxy-16,16-difluoro-PGE₁, a prostacyclin analog according to claim
 29. 31. A prostacyclin analog according to claim 28, wherein at least one of R₃ and R₄ is methyl.
 32. 11-Deoxy-11-hydroxymethyl-6-hydroxy-16,16-dimethyl-PGE₁, a prostacyclin analog according to claim
 31. 33. A prostacyclin analog according to claim 28, wherein R₃ and R₄ are both hydrogen.
 34. 11-Deoxy-11-hydroxymethyl-6-hydroxy-PGE₁, methyl ester, a prostacyclin analog according to claim
 33. 35. 11-Deoxy-11-hydroxymethyl-6-hydroxy-PGE₁, tris(hydroxymethyl)aminomethane salt, a prostacyclin analog according to claim
 33. 36. 11-Deoxy-11-hydroxymethyl-6-hydroxy-PGE₁, benzamidophenyl ester, a prostacyclin analog according to claim
 33. 37. 11-Deoxy-11-hydroxymethyl-6-hydroxy-PGE₁, a prostacyclin analog according to claim
 33. 